Depression is the most common co-morbid condition in epilepsy, affecting between 20-55% of patients with refractory epilepsy and 3-9% of patients with well-controlled seizures. The combination of epilepsy and affective disorders has been associated in multiple studies with diminished quality of life, increased healthcare utilization, and increased suicidal ideation and attempts. The cause of this co-morbidity is unknown. This co-morbidity may be due, in part, to a psychological reaction to having a chronic, stigmatizing disorder. However, another possibility is a shared genetic susceptibility to both disorders. The broad goal of this study is to test this shared genetic etiology hypothesis. Based on prior research, I hypothesize that the lifetime prevalence of affective disorders is higher in unaffected siblings from familial epilepsy pedigrees than in the general population. The hypotheses will be tested through a series of genetic epidemiological studies to distinguish between reactive effects and shared genetic susceptibility. I will also examine the co- morbidity of epilepsy and affective disorders within clinically defined subgroups of epilepsy; in particular, I will test the hypothesis that risk of affective disorders is increased in primary generalized epilepsy, as well as in focal epilepsy. Reliable and valid measures will be used to assess a lifetime prevalence of affective disorders. Identifying that shared etiology accounts for some of the co-morbidity between epilepsy and affective disorders could help identify individuals at high-risk for both disorders, allow for early intervention, and provide a model for understanding epilepsy neurobiology. Positive results may also provide an impetus for improved assessment and management of affective disorders by neurologists treating people with epilepsy. Future studies, using the refined phenotype definitions in the specific subtypes, could also be designed to locate genes. The goal of this study is consistent with the NINDS "Benchmarks" for Epilepsy Research: "Continue the progress of identifying the genes predisposing to epilepsy." It also parallels several active Program Announcements from NINDS: (PA Number: PA-03-169) entitled "Basic and Translational Research in Emotion"; (PA Number: PA-02-111) entitled "Self-Management Strategies Across Chronic Diseases"; and (PA Number: PAS-03-092) entitled "Gene Discovery For Complex Neurological And Neurobehavioral Disorders." [unreadable] [unreadable] [unreadable]